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Nevin Manimala Statistics

CARD 2023: expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database

Nucleic Acids Res. 2022 Oct 20:gkac920. doi: 10.1093/nar/gkac920. Online ahead of print.

ABSTRACT

The Comprehensive Antibiotic Resistance Database (CARD; card.mcmaster.ca) combines the Antibiotic Resistance Ontology (ARO) with curated AMR gene (ARG) sequences and resistance-conferring mutations to provide an informatics framework for annotation and interpretation of resistomes. As of version 3.2.4, CARD encompasses 6627 ontology terms, 5010 reference sequences, 1933 mutations, 3004 publications, and 5057 AMR detection models that can be used by the accompanying Resistance Gene Identifier (RGI) software to annotate genomic or metagenomic sequences. Focused curation enhancements since 2020 include expanded β-lactamase curation, incorporation of likelihood-based AMR mutations for Mycobacterium tuberculosis, addition of disinfectants and antiseptics plus their associated ARGs, and systematic curation of resistance-modifying agents. This expanded curation includes 180 new AMR gene families, 15 new drug classes, 1 new resistance mechanism, and two new ontological relationships: evolutionary_variant_of and is_small_molecule_inhibitor. In silico prediction of resistomes and prevalence statistics of ARGs has been expanded to 377 pathogens, 21,079 chromosomes, 2,662 genomic islands, 41,828 plasmids and 155,606 whole-genome shotgun assemblies, resulting in collation of 322,710 unique ARG allele sequences. New features include the CARD:Live collection of community submitted isolate resistome data and the introduction of standardized 15 character CARD Short Names for ARGs to support machine learning efforts.

PMID:36263822 | DOI:10.1093/nar/gkac920

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Sudden cardiac death risk prediction in arrhythmogenic right ventricular cardiomyopathy: the challenge of complex statistical modelling and its impact in clinical practice

Eur Heart J. 2022 Oct 20:ehac538. doi: 10.1093/eurheartj/ehac538. Online ahead of print.

NO ABSTRACT

PMID:36263796 | DOI:10.1093/eurheartj/ehac538

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Non-Invasive Vascular Elastography as a One-Step Imaging Technique to Evaluate Early Vascular Changes in Children Compared to B-Mode-Based Intima-Media Thickness Technique : A Validation Study Using Inter- and Intra-Rater Reliability

Can Assoc Radiol J. 2022 Oct 20:8465371221134055. doi: 10.1177/08465371221134055. Online ahead of print.

ABSTRACT

Background: Childhood obesity is linked to higher adult mortality and morbidity from atherosclerosis. It is primordial to detect at-risk children earlier-on to prevent disease progression. Carotid intima-media thickness (IMT) is a subclinical radiological marker for early atherosclerosis. B-mode ultrasound is a known technique to assess IMT, but no gold standard technique exists in children. Non-invasive vascular elastography (NIVE) using speckle statistics is an innovative alternative to evaluate IMT and adds by providing translation, strain and shear strain measurements. Validation studies for both techniques lack in children. Purpose: Validate the reproducibility of the 2 techniques in Canadian children. Methods: We conducted a prospective study where anthropometry, blood pressure, IMT and elastography were measured. Six operators obtained 2 measurements for both carotid arteries using both techniques, for a total of 720 measurements. Inter- and intra-class correlation coefficients (ICC) were calculated for each measurement technique and elastography parameters. Results: 30 participants (13.0 ± 1.26 years, 17 girls) were recruited. Twelve were overweight. No significant difference was found in mean IMT between weight groups for either technique (P = .15 and P = .60). We found excellent inter- (ICC = .98 [95% Confidence Interval (CI): .97; .99]) and intra- (ICC = .90-.93) operator reliability for the B-mode technique, and good inter (ICC = .70 [95% CI: .47; .85]) and intra- (ICC = .71-.91) operator reliability for the NIVE-based technique. Poor reliability was found between techniques (ICC = .30 [95% CI: -.31; .65). For elastography parameters, translation was the most reliable (ICC = .94-.95). Conclusion: IMT measurement is reproducible in children but not between techniques. NIVE gives the advantage of evaluating elastography.

PMID:36263774 | DOI:10.1177/08465371221134055

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Relationship between healthy lifestyle behaviours and subjective wellbeing: an european observational study.

Rev Esp Salud Publica. 2022 Oct 19;96:e202210078.

ABSTRACT

OBJECTIVE: A healthy lifestyle is related to physical and mental health. The aim of this study was to assess whether different healthy lifestyle behaviours are associated with experiential and evaluative well-being.

METHODS: A total of 10,800 participants from Finland, Poland and Spain were interviewed in 2011-2012. Physical activity, fruit and vegetable consumption, smoking, alcohol use, and sleep quality were self-reported. Life satisfaction was measured with the Cantril Self-Anchoring Striving Scale. Positive and negative affect were assessed using an abbreviated version of the Day Reconstruction Method. Multivariate regression analyses were performed.

RESULTS: Healthy lifestyle behaviours (consumption of five or more servings of fruit and vegetables per day, moderate or high physical activity, being a non-daily smoker, and having a good sleep quality) were positively associated with evaluative well-being (ß=0.23 p<0.001; ß=0.16, p<0.001; ß=0.26, p<0.001; ß=0.23, p<0.001, respectively), after controlling for confounding variables such as health and depression. Good sleep quality was related with higher positive affect (ß=0.29, p<0.001), lower negative affect (ß=-0.15, p<0.001) and higher life satisfaction (ß=0.23, p<0.001), after adjusting for those confounding variables.

CONCLUSIONS: A healthy lifestyle is an important correlate of well-being independently of its effects on health. Healthy lifestyles could be considered when developing strategies to improve not only the physical health, but also the well-being of the population.

PMID:36263753

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Evaluation of P53 protein expression in gingival tissues of patients with chronic periodontitis by immunohistochemistry methods

Clin Exp Dent Res. 2022 Oct 20. doi: 10.1002/cre2.668. Online ahead of print.

ABSTRACT

OBJECTIVE: Periodontitis is one of the most important periodontal diseases that can be affected by many factors. Although the mechanism of periodontitis development is not yet fully understood, previous studies suggest that apoptosis may be one of the pathological factors that can affect the process of the disease by destroying old and damaged cells. Low expression of P53 protein is one of the reasons for delaying cell death that allows damaged cells to survive longer and gives more time for the chance of mutations and pathogenesis. Because of the important role of P53 in gingival cells of patients with chronic periodontitis, the objective of our study is to evaluate the P53 protein expression in gingival tissues of patients with chronic periodontitis by immunohistochemistry methods.

MATERIALS AND METHODS: In this cross-sectional study, 35 patients with severe to moderate chronic periodontitis (loss of attachment ≥3 mm, probing depth ≥5 mm) with no treatment and 25 people who were healthy for periodontal problems were examined. Gingival biopsies from marginal and attached gingiva were obtained, prepared, and mounted on slides. Then, the expression of P53 on each slide was evaluated by optic microscopy after using P53 antibodies and staining with hematoxylin-eosin (immunohistochemistry method). Data were analyzed using independent t-test, Mann-Whitney U-test, and Spearman correlation test using SPSS Statistics version 18.0.

RESULTS: The mean ages of participants in the case and control groups were 37.58 and 32.09, respectively. Our results showed that the expression of P53 was not significant in periodontitis compared to the control group (p > .05). Also, gender could not affect the expression of P53 in both groups (p > .05), and there was no significant relationship between age and P53 gene incidence.

CONCLUSION: Chronic periodontitis has no significant effect on P53 expression, so changes in apoptosis due to P53 expression in periodontitis are not significant.

PMID:36263737 | DOI:10.1002/cre2.668

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Treatment and biologic maintenance-dosing patterns among pediatric patients with ulcerative colitis or Crohn’s disease

Curr Med Res Opin. 2022 Oct 20:1-19. doi: 10.1080/03007995.2022.2135836. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess treatment patterns and initial and maintenance dosing of biologics over 3 years in pediatric patients with ulcerative colitis (UC) or Crohn’s disease (CD), utilizing data from the ImproveCareNow registry.

METHODS: Pediatric patients diagnosed with UC or CD and aged 2-17 years were included in the study. Descriptive statistics were employed to summarize baseline demographics. The proportion of patients on medication for UC or CD were analyzed at the baseline visit, 1-year, and 3-year time points (Cohort 1). Biologic maintenance dosage was calculated only for patients who had data for dose and weight at all time points (Cohort 2).

RESULTS: In Cohort 1 (UC =1784; CD =4720), baseline treatment in UC included corticosteroid, 5-ASA, and 6-MP/AZA; at 1-year and 3-year time points, treatment with 5-ASA and corticosteroid decreased, whereas 6-MP/AZA and anti-TNFs increased. In CD, baseline treatment included corticosteroid, anti-TNF, 6-MP/AZA, and methotrexate; use of corticosteroids decreased, whereas the use of methotrexate and anti-TNFs increased over 3 years. In Cohort 2 (UC =350; CD =1,537), at first maintenance dose, UC patients on infliximab received a mean dose of 10.5mg/kg/8wk, adalimumab (weight <40kg and ≥40kg) 1.3mg/kg/2wk and 0.8mg/kg/2wk, and vedolizumab 6.9mg/kg/8wks. At the first maintenance dose, CD patients on infliximab received a mean dose of 8.1mg/kg/8wk, adalimumab (weight <40kg) 1.1mg/kg/2wk, adalimumab (weight ≥40kg) 0.8mg/kg/2wk, and vedolizumab 10.5mg/kg/8wks.

CONCLUSION: The use of corticosteroids was common at the initial visit in patients. Anti-TNFs remain the most used class of biologics, however, reported doses in our study were substantially higher than the standard dosing guidelines.

PMID:36263735 | DOI:10.1080/03007995.2022.2135836

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Impact of COVID-19 on HIV late diagnosis in a specialized German centre

HIV Med. 2022 Oct 20. doi: 10.1111/hiv.13426. Online ahead of print.

ABSTRACT

BACKGROUND: The ongoing COVID-19 pandemic has been impeding HIV diagnosis and treatment worldwide. Data on the impact of COVID-19 on late diagnosis (LD) in Germany are lacking. Here we present novel data of a single-centre German HIV cohort assessing LD during COVID-19.

METHODS: This is a non-interventional, single-centre retrospective cohort assessing the rate of LD comparing HIV diagnoses pre-COVID-19 with those during the COVID-19 pandemic. New diagnoses between 1 January 2019 and 1 February 2020 were classified as pre-COVID-19, and diagnoses between 1 February 2020 and 1 October 2021 were classified as during COVID-19.

RESULTS: Between 1 January 2019 and 1 October 2021, 75 patients presented with newly diagnosed HIV infection, 34 pre-COVID-19 and 41 during COVID-19. LD increased to 83% (n = 34/41) during COVID-19 versus 59% (n = 20/34) pre-COVID-19, and CDC stage C3 rose to 44% (n = 18) versus 27%. Hospitalization rate increased to 49% (n = 20) during COVID-19 versus 29% pre-COVID-19, and 12% (n = 5) presented with HIV-associated neurological disease, whereas none were observed in the pre-COVID-19 group. The incidence of LD (p = 0.020), CD4 count < 350 cells/μL (p = 0.037) and < 200 cells/μL (p = 0.022) were statistically significantly associated with the ongoing COVID-pandemic. An association with HIV transmission risk was borderline significant (p = 0.055).

CONCLUSIONS: Despite comparable annual rates of new HIV diagnoses, LD has been increasing during the COVID-19 pandemic, resulting in more opportunistic infections and higher hospitalization rates, possibly reflecting pandemic-related shortages in HIV testing and care facilities. Maintaining HIV testing opportunities and access to treatment during a pandemic is crucial so as not to impede WHO elimination goals and so as to prevent an increase in AIDS-related morbidity and mortality.

PMID:36263724 | DOI:10.1111/hiv.13426

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Management and Outcomes of Salmonella Gastroenteritis in the Era of Rapid Molecular Testing

Hosp Pediatr. 2022 Oct 20:e2021006450. doi: 10.1542/hpeds.2021-006450. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Molecular diagnostics provide a rapid and sensitive diagnosis of gastroenteritis compared with a stool culture. In this study, we seek to describe the changes in medical management and outcomes of children with Salmonella gastroenteritis as our hospital system adopted molecular diagnostics.

METHODS: This study is a retrospective chart review of children <18 years of age diagnosed with nontyphoidal Salmonella gastroenteritis between 2008 and 2018 at a large pediatric health care system in the southeastern United States. Those with immunocompromising conditions and hemoglobinopathies were excluded. Patients diagnosed via molecular testing were compared with those diagnosed solely by stool culture for aspects of management including admission rates, blood culture obtainment, and antibiotic administration.

RESULTS: Of 965 eligible patients with Salmonella gastroenteritis, 264 (27%) had a stool molecular test and 701 (73%) only had a stool culture performed. Groups were similar in age and presentation. Those diagnosed by molecular methods had higher hospitalization rates (69% vs 50%, P <.001), more blood cultures obtained (54% vs 44%, P <.01), and received more antibiotics (49% vs 34%, P <.001) despite statistically similar rates of bacteremia (11% vs 19%, P = .05).

CONCLUSIONS: The rapid diagnosis of Salmonella gastroenteritis by molecular methods was associated with increased hospital admission rates, blood culture obtainment, and antibiotic use. This suggests possible overmedicalization of uncomplicated Salmonella gastroenteritis, and clinicians should remain cognizant of the possibility of providing low-value care for uncomplicated disease.

PMID:36263712 | DOI:10.1542/hpeds.2021-006450

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Propolis supplementation in obese patients with non-alcoholic fatty liver disease: effects on glucose homeostasis, lipid profile, liver function, anthropometric indices and meta-inflammation

Food Funct. 2022 Oct 20. doi: 10.1039/d2fo01280d. Online ahead of print.

ABSTRACT

This study assessed the effects of propolis supplementation on glucose homeostasis, lipid profile, liver function, anthropometric indices and meta-inflammation in patients with non-alcoholic fatty liver disease (NAFLD). In this double-blind placebo-controlled randomized clinical trial, 44 patients with NAFLD confirmed by ultrasonography findings were randomly allocated into either the “propolis” (n = 23) or “placebo” (n = 21) group along with a calorie-restricted diet (-500 kcal d-1) for 8 weeks. Fasting serum levels of metabolic factors, liver enzymes, and inflammatory factors, as well as anthropometric indices, dietary intake and appetite status were assessed pre-and post-intervention. The liver fibrosis score, homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were also calculated. The weight, body mass index (BMI), waist and hip circumferences, and waist to height ratio significantly decreased in both groups (p < 0.001), while the waist to hip ratio (p = 0.006) and serum level of total cholesterol (p = 0.038) decreased only in the propolis arm. However, no significant changes in anthropometric measurements and lipid profile were found between the groups at the end of the intervention. Fasting blood sugar (p = 0.037), the serum insulin level (p = 0.040), HOMA-IR (p = 007), desire to eat sweet foods (p = 0.005) and the NAFLD fibrosis score (p = 0.013) decreased significantly in the propolis group compared to the placebo group, post-intervention after adjusting for baseline values and potential confounders. However, QUICKI showed a significant increase (p = 0.015) in the propolis arm compared to the placebo at the study endpoint. Although there were significant reductions in the serum levels of inflammatory factors including tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR-4) and monocyte chemoattractant protein-1 (MCP-1), as well as liver enzymes and severity of fatty liver, between-group differences were not statistically significant after adjusting for the potential confounding factors. The estimated number needed to treat (NNT) due to 8-week propolis supplementation (510 mg per day) for at least 1-point improvement in NAFLD severity was found to be approximately 3. In conclusion, propolis supplementation along with a calorie-restricted diet for 8 weeks could significantly improve the glucose homeostasis, hepatic fibrosis score and liver function in patients with NAFLD. Further clinical trials are encouraged to study the effects of propolis supplementation in patients with long-term NAFLD.

PMID:36263703 | DOI:10.1039/d2fo01280d

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Association between Systemic Lupus Erythematosus and Primary Hypothyroidism: evidence from complementary genetic methods

J Clin Endocrinol Metab. 2022 Oct 20:dgac614. doi: 10.1210/clinem/dgac614. Online ahead of print.

ABSTRACT

INTRODUCTION: Systemic lupus erythematosus (SLE) and hypothyroidism often coexist in observational studies; however, the causal relationship between them remains controversial.

METHODS: Complementary genetic approaches, including genetic correlation, Mendelian randomization (MR) and colocalization analysis, were conducted to assess the potential causal association between SLE and primary hypothyroidism using summary statistics from large-scale genome-wide association studies (GWASs). The association between SLE and thyroid-stimulating hormone (TSH) was further analyzed to help interpret the findings. In addition, findings were verified using a validation dataset, as well as through different MR methods with different model assumptions.

RESULTS: The linkage disequilibrium score regression revealed a shared genetic structure between SLE and primary hypothyroidism, with the significant genetic correlation estimated to be 0.2488 (p = 6.00 × 10-4). MR analysis with the inverse variance weighted (IVW) method demonstrated a bidirectional causal relationship between SLE and primary hypothyroidism. The odds ratio (OR) of SLE on primary hypothyroidism was 1.037 (95% CI, 1.013-1.061; p = 2.00 × 10-3) and that of primary hypothyroidism on SLE was 1.359 (95% CI, 1.217-1.520; p < 0.001). The OR of SLE on TSH was 1.007 (95% CI, 1.001-1.013; p = 0.032) .However, TSH was not causally associated with SLE (p = 0.152). Similar results were found using different MR methods. In addition, colocalization analysis suggested that shared causal variants existed between SLE and primary hypothyroidism. The results of the validation analysis indicated a bidirectional causal relationship between SLE and primary hypothyroidism, as well as shared loci.

CONCLUSION: In summary, a bidirectional causal relationship between SLE and primary hypothyroidism was observed with complementary genetic approaches.

PMID:36263677 | DOI:10.1210/clinem/dgac614